本文選題：甲醛 + 過敏性哮喘��； 參考：《華中師范大學》2013年博士論文

【摘要】：甲醛是一種常見的裝修型化學性室內(nèi)空氣污染物,也是一種全球性的環(huán)境污染物。它具有污染來源廣、時間長、水平高、毒性種類多等特點。甲醛對健康的影響主要包括：呼吸道和眼部急性刺激作用、神經(jīng)行為改變、生殖毒性、免疫毒性、氧化損傷、遺傳毒性等諸多方面。近年來,世界各地哮喘發(fā)病率都在快速增長,但致敏原的種類和數(shù)量并未發(fā)生顯著變化。非過敏原性空氣污染物的大量增加被認為是原因之一,但其分子機制尚不清楚。不斷有研究表明,甲醛暴露可以引起哮喘或哮喘樣癥狀。為了探討甲醛是否可以誘發(fā)哮喘和其可能的發(fā)病機理,本論文進行了如下體內(nèi)研究： 1.甲醛導致中樞神經(jīng)系統(tǒng)神經(jīng)源性炎癥及氧化性損傷發(fā)生：對Balb/c小鼠連續(xù)甲醛氣態(tài)暴露7天,每天8小時,設(a)對照組；(b)0.5mg/m3甲醛組；(c)3.0mg/m3甲醛組,在3.0mg/m3水平甲醛作用下,與對照組相比較：(1)腦組織谷胱甘肽(GSH)含量呈極顯著性降低(p0.01),脊髓組織GSH含量呈顯著性降低(p0.05)；(2)腦組織丙二醛(MDA)含量呈極顯著性增高(p0.01),脊髓組織MDA含量呈顯著性增高(p0.05)；(3)腦組織促炎癥細胞因子白介素-IL-1β含量呈顯著性增高(p0.05),脊髓組織IL-1β含量呈極顯著性增高(p0.01)；(4)腦組織速激肽物質P含量(substance P)呈極顯著增高(p0.01),脊髓組織substance P含量呈極顯著性增高(p0.01)。本實驗說明甲醛可以導致中樞神經(jīng)系統(tǒng)神經(jīng)性炎癥及氧化損傷發(fā)生。 2. TRPA1介導甲醛所致氣道炎癥發(fā)生：對Balb/c小鼠連續(xù)甲醛氣態(tài)暴露10天,每天8小時。設(a)對照組；(b)0.5mg/m3甲醛組；(c)1.0mg/m3甲醛組；(d)3.0mg,/m3甲醛組；(e)3.0mg/m3+HC-030031[瞬時受體電位通道亞型A1(TRPA1)拮抗劑]組,發(fā)現(xiàn)在3.0mg/m3甲醛水平作用下,與對照組相比較：(1)血清中免疫球蛋白E(1gE)水平顯著上升(p0.01)；(2)小鼠肺泡灌洗液中白介素-4(IL-4)含量顯著上調(p0.01)；(3)血清中超氧化物歧化酶(SOD)活力顯著下降(p0.01),MDA含量顯著上升(p0.01)；對3.0mg/m3甲醛給予HC-030031(50mg/kg)處理,發(fā)現(xiàn)IgE水平下調(p0.01),IL-4水平下調(p0.01), SOD活力上升(p0.05),MDA含量下降(p0.05)；本實驗說明TRPA1可以介導甲醛所致氣道炎癥發(fā)生和氧化損傷作用。 3. TRPA1和TRPV1通道蛋白介導氣態(tài)甲醛誘導哮喘作用：對Balb/c雄性小鼠甲醛動態(tài)式氣態(tài)暴露4周,每天6小時,卵清蛋白(OVA)致敏并激發(fā)1周建立甲醛誘導哮喘模型。設(a)對照組；(b) OVA組；(c)3.0mg/m3甲醛組；(d)3.Omg/m3甲醛+OVA組；(e)3.0mg/m3甲醛+OVA+HC-030031組；(f)3.0mg/m3甲醛+OVA+capsazepine(瞬時受體電位通道亞型V1拮抗劑)組,分別測定氣道高反應性、氣道重塑、氣道炎癥相關指標。與對照組相比,甲醛組氣道反應性和肺部病理學變化并不明顯,但嗜酸性粒細胞計數(shù)顯著增高(p0.05),血清總IgE含量明顯上調(p0.01),IL-4含量顯著升高(p0.01), substance P表達上調(p0.01),降鈣素基因相關肽(CGRP)表達上調(p0.05),IL-1p水平升高(p0.01)；與OVA組相比,甲醛+OVA組呈現(xiàn)顯著氣道高反應性和氣道重塑現(xiàn)象,嗜酸性粒細胞計數(shù)顯著增高(p0.01),血清中總IgE水平顯著上調(p0.01),肺組織IL-4含量顯著升高(p0.01)；substance P表達上調(p0.01)、CGRP表達上調(p0.01), IL-1β水平升高(p0.01)。對FA+OVA組給予TRPA1通道拮抗劑HC-030031和TRPV1通道拮抗劑CPZ,結果顯示：拮抗組與模型組相比,(1)氣道高反應性顯著降低：(2)肺組織病理變化明顯好轉；(3)小鼠肺泡灌洗液中嗜酸性粒細胞計數(shù)降低(p0.01),肺組織IL-4含量顯著降低(p0.01),血清中IgE水平降低(p0.01)；(4)substance P表達下調(p0.01)、CGRP表達下調(p0.05), IL-1β水平無顯著變化(p0.05)。結果說明甲醛可以提高哮喘的發(fā)病風險,它可以直接導致神經(jīng)源性氣道炎癥,并以免疫佐劑身份加重OVA過敏原導致氣道炎癥；Substance P和CGRP參與甲醛誘導哮喘的病理生理過程,TRPA1和TRPV1通道蛋白介導氣態(tài)甲醛誘導哮喘作用并調控神經(jīng)肽的釋放。
[Abstract]:Formaldehyde is a common decoration chemical indoor air pollutant and a global environmental pollutant. It has a wide range of pollution sources, long time, high level, and many toxic types. The effect of formaldehyde on health mainly includes: respiratory and ocular acute stimulation, neurobehavioral changes, reproductive toxicity, immunotoxicity, oxygen, and oxygen. In recent years, the incidence of asthma in all parts of the world has been growing rapidly, but the variety and number of allergens have not changed significantly. A large increase in non allergen air pollutants is considered to be one of the reasons, but its molecular mechanism is not clear. Asthma or asthma like symptoms. In order to investigate whether formaldehyde can induce asthma and its possible pathogenesis, the following studies were carried out in vivo.
1. formaldehyde caused neurogenic inflammation and oxidative damage in the central nervous system: 7 days of continuous formaldehyde exposure to Balb/c mice, 8 hours a day, (a) control group; (b) 0.5mg/m3 formaldehyde group; (c) 3.0mg/m3 formaldehyde group and compared with the control group under the action of 3.0mg/m3 level formaldehyde: (1) the content of glutathione (GSH) in the brain tissue was extremely significant The content of GSH in spinal cord tissue decreased significantly (P0.05), and (2) the content of malondialdehyde (MDA) in the brain tissue was significantly increased (P0.01), and the content of MDA in the spinal cord tissue was significantly increased (P0.05) (P0.05); (3) the content of interleukin -IL-1 beta in the brain tissue was significantly increased (P0.05), and the content of IL-1 beta in the spinal tissue was very significant. Increase (P0.01); (4) the content of P (substance P) of the brain tissue tachykinin (substance P) was significantly increased (P0.01), and the content of substance P in the spinal cord was significantly increased (P0.01). This experiment showed that formaldehyde could lead to neurogenic inflammation and oxidative damage in the central nervous system.
2. TRPA1 mediated formaldehyde induced airway inflammation: 10 days of continuous formaldehyde exposure to Balb/c mice, 8 hours a day. (a) control group; (b) 0.5mg/m3 formaldehyde group; (c) 1.0mg/m3 formaldehyde group; (d) 3.0mg, /m3 formaldehyde group; (E) 3.0mg/m3+HC-030031[instantaneous receptor channel subtype antagonist] group, found in formaldehyde level Under the action, compared with the control group, (1) the serum level of immunoglobulin E (1gE) increased significantly (P0.01); (2) the content of interleukin -4 (IL-4) in the mouse alveolar lavage was significantly up (P0.01); (3) the activity of superoxide dismutase (SOD) in the serum decreased significantly (P0.01) and MDA increased significantly (P0.01), and HC-030031 (P0.01) was given to 3.0mg/m3 formaldehyde (P0.01). /kg) treatment, IgE level down (P0.01), IL-4 level down (P0.01), SOD activity (P0.05) and MDA content decreased (P0.05). This experiment shows that TRPA1 can mediate the effect of formaldehyde induced airway inflammation and oxidative damage.
3. TRPA1 and TRPV1 channel proteins mediate the effect of gaseous formaldehyde induced asthma: for 4 weeks of formaldehyde dynamic exposure in Balb/c male mice, 6 hours a day, ovalbumin (OVA) sensitization and excitation of formaldehyde induced asthma model. Set (a) control group; (b) OVA group; (c) 3.0mg/m3 formaldehyde group; (d) 3.Omg/m3 formaldehyde +OVA group; (d) 3.Omg/m3 formaldehyde +OVA group; (d) 3.Omg/m3 formaldehyde +OVA group; (d) 3.Omg/m3 formaldehyde +OVA group; Group +OVA+HC-030031; (f) 3.0mg/m3 formaldehyde +OVA+capsazepine (transient receptor potential channel subtype V1 antagonist), the airway hyperresponsiveness, airway remodeling, airway inflammation related indexes respectively. Compared with the control group, the airway reactivity and pulmonary pathological changes were not obvious in the control group, but the eosinophil count increased significantly (P0.05). The content of IgE was obviously up (P0.01), the content of IL-4 increased significantly (P0.01), the expression of substance P was up (P0.01), the expression of calcitonin gene related peptide (CGRP) up up (P0.05), IL-1p level increased (P0.01). Compared with the OVA group, the formaldehyde group showed significant airway hyperresponsiveness and airway remodeling, and the eosinophil count increased significantly. The total IgE level in the serum was significantly up-regulated (P0.01), the IL-4 content in the lung tissue was significantly increased (P0.01), the expression of substance P was up (P0.01), the expression of CGRP was up (P0.01), and the IL-1 beta level increased (P0.01). The results showed that the antagonist and the channel antagonist were compared with the model group, (1) the hyperreaction of the airway. (2) the pathological changes of lung tissue were obviously improved; (3) the eosinophil count in the alveolar lavage fluid in mice decreased (P0.01), the IL-4 content in the lung tissue decreased significantly (P0.01), the level of IgE in the serum decreased (P0.01); (4) the downregulation of substance P (P0.01), CGRP expression down (P0.05), IL-1 beta level had no significant changes (P0.05). The results said It can improve the risk of asthma, which can directly cause neurogenic airway inflammation and aggravate the OVA allergen in airway inflammation with an immune adjuvant. Substance P and CGRP are involved in the pathophysiological process of formaldehyde induced asthma. TRPA1 and TRPV1 channel proteins mediate the effect of gaseous formaldehyde to induce asthma and regulate neuropeptides. Release.
【學位授予單位】：華中師范大學
【學位級別】：博士
【學位授予年份】：2013
【分類號】：R114;R562.25

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